Purpose: To present a case of refractory systemic lupus erythematosus (SLE)-associated retinal vasculitis that responded to the anti-tumor necrosis factor (TNF)-alpha inhibitor adalimumab as corticosteroid-sparing therapy. Methods: Descriptive case report of a patient with SLE with retinal vasculitis complicated by an ischemic retinal vein occlusion and cystoid macular edema. Results: A 30-year-old female patient with a history of SLE presented with retinal vasculitis and an ischemic, branch retinal vein occlusion with macular edema in the left eye. Oral corticosteroid was administered along with mycophenolate mofetil (MMF) as a corticosteroid-sparing agent. Despite MMF therapy, the patient developed an exacerbation of her vasculitis with the involvement of both eyes. Adalimumab was initiated with a resultant resolution of retinal vasculitis as a corticosteroid-sparing strategy with over 2 years of follow-up. Conclusion: Anti-TNF-alpha therapy with adalimumab may be effective as a corticosteroid-sparing agent in select patients with ocular inflammation associated with SLE.
by
Jessica Shantha;
John G. Mattia;
Augustine Goba;
Kayla G. Barnes;
Faiqa K. Ebrahim;
Colleen S Kraft;
Brent R. Hayek;
Jessica N. Hartnett;
Jeffrey G. Shaffer;
John S. Schieffelin;
John D. Sandi;
Mambu Momoh;
Simbirie Jalloh;
Donald S. Grant;
Kerry Dierberg;
Joyce Chang;
Sharmistha Mishra;
Adrienne K. Chan;
Rob Fowler;
Tim O'Dempsey;
Erick Kaluma;
Taylor Hendricks;
Roger Reiners;
Melanie Reiners;
Lowell A. Gess;
Kwame ONeill;
Sarian Kamara;
Alie Wurie;
Mohamed Mansaray;
Nisha R. Acharya;
William J. Liu;
Sina Bavari;
Gustavo Palacios;
Moges Teshome;
Ian Crozier;
Paul E. Farmer;
Timothy M. Uyeki;
Daniel G. Bausch;
Robert F. Garry;
Matthew J. Vandy;
Steven Yeh
Background: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. Methods: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). Findings: We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P < 0.001). Interpretation: EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.
by
John A. Gonzales;
Armin Hinterwirth;
Jessica Shantha;
Kaida Wang;
Lina Zhong;
Susie L. Cummings;
Ying Qian;
Micheal R. Wilson;
Nisha R. Acharya;
Doan Thuy
Importance: Metagenomic deep sequencing (MDS) demonstrates that persistent and active rubella virus (RV) infection is associated with Fuchs heterochromic iridocyclitis (FHI).
Objective: To assess the utility of MDS in identifying RV infection in patients with uveitis. Design, Setting, and Participants: This case series assessed 6 patients diagnosed by MDS with RV-associated uveitis at a tertiary uveitis referral center in the United States.
Exposures: Prior RV infection.
Main Outcomes and Measures: Clinical examination findings, slitlamp photography, corneal confocal imaging, and infectious pathogen genome obtained from RNA sequencing.
Results: Six white men (age range, 36-61 years) were diagnosed with RV-associated uveitis by MDS. Three patients exhibited iris heterochromia associated with their uveitis in classic FHI fashion. The other 3 patients had less classic FHI features and exhibited anterior vitritis. Three patients had in vivo corneal confocal microscopy, with 2 demonstrating stellate keratic precipitates in addition to endothelial infiltration, spotlike holes, and enlarged intercellular boundaries. Of these 3 patients, 1 patient exhibited polymorphism and polymegathism of the endothelial cells.
Conclusions and Relevance: These findings suggest that persistent RV infection is associated with recurrent or chronic anterior or anterior-intermediate uveitis as well as corneal endothelial cell damage. Ophthalmologists should consider RV infection as a potential cause of hypertensive anterior and intermediate uveitis.
BACKGROUND: In the wake of the West African Ebola virus disease (EVD) outbreak of 2014-2016, thousands of EVD survivors began to manifest a constellation of systemic and ophthalmic sequelae. Besides systemic arthralgias, myalgias, and abdominal pain, patients were developing uveitis, a spectrum of inflammatory eye disease leading to eye pain, redness, and vision loss. To investigate this emerging eye disease, resources and equipment were needed to promptly evaluate this sight-threatening condition, particularly given our identification of Ebola virus in the ocular fluid of an EVD survivor during disease convalescence. METHODOLOGY/PRINCIPAL FINDINGS: A collaborative effort involving ophthalmologists, infectious disease specialists, eye care nurses, and physician leadership at Eternal Love Winning Africa (ELWA) Hospital in Liberia led to the development of a unique screening eye clinic for EVD survivors to screen, treat, and refer patients for more definitive care. Medications, resources, and equipment were procured from a variety of sources including discount websites, donations, purchasing with humanitarian discounts, and limited retail to develop a screening eye clinic and rapidly perform detailed ophthalmologic exams. Findings were documented in 96 EVD survivors to inform public health officials and eye care providers of the emerging disease process. Personal protective equipment was tailored to the environment and implications of EBOV persistence within intraocular fluid. CONCLUSIONS/SIGNIFICANCE: A screening eye clinic was feasible and effective for the rapid screening, care, and referral of EVD survivors with uveitis and retinal disease. Patients were screened promptly for an initial assessment of the disease process, which has informed other efforts within West Africa related to immediate patient care needs and our collective understanding of EVD sequelae. Further attention is needed to understand the pathogensis and treatment of ophthalmic sequelae given recent EVD outbreaks in West Africa and ongoing outbreak within Democratic Republic of Congo.
Ebola virus disease (EVD) and emerging infectious disease threats continue to threaten life, prosperity and global health security. To properly counteract EVD, an improved understanding of the long-term impact of recent EVD outbreaks in West Africa and the Democratic Republic of Congo are needed. In the wake of recent outbreaks, numerous health sequelae were identified in EVD survivors. These findings include joint pains, headaches, myalgias, and uveitis, a vision-threatening inflammatory condition of the eye. Retrospective and more recent prospective studies of EVD survivors from West Africa have demonstrated that uveitis may occur in 13-34% of patients with an increase in prevalence from baseline to 12-month follow-up. The clinical spectrum of disease ranges from mild, anterior uveitis to severe, sight-threatening panuveitis.
Untreated inflammation may ultimately lead to secondary complications of cataract and posterior synechiae, with resultant vision impairment. The identification of Ebola virus persistence in immune privileged organs, such as the eye, with subsequent tissue inflammation and edema may lead to vision loss. Non-human primate models of EVD have demonstrated tissue localization to the eye including macrophage reservoirs within the vitreous matter. Moreover, in vitro models of Ebola virus have shown permissiveness in retinal pigment epithelial cells, potentially contributing to viral persistence. Broad perspectives from epidemiologic studies of the outbreak, animal modeling, and immunologic studies of EVD survivors have demonstrated the spectrum of the eye disease, tissue specificity of Ebola virus infection, and antigen-specific immunologic response. Further studies in these areas will elucidate the mechanisms of this highly prevalent disease with the potential for improved therapeutics for Ebola virus in immune-privileged sites.
Introduction: Optic capture of sutured scleral fixated posterior chamber intraocular lenses (PC IOLs) is an occasional complication resulting in blurred vision and discomfort. Methods: A retrospective study of the management of 18 eyes (3.6%) with optic capture out of 495 eyes with scleral fixated IOLs during the study period. 54 procedures were performed in the management of optic capture of sutured scleral fixated PC IOLs. An in-office technique was utilized to relieve the optic capture by repositioning the optic posterior to the iris. This technique was performed after topical anesthesia and topical 5% betadine with the patient stably positioned at the slit lamp. Using a 30-gauge needle, sometimes after a 15-degree paracentesis blade, the needle was advanced in a parallel plane above the iris until the tip reached the edge of the captured optic. The optic is engaged in the inferior periphery away from the central visual axis, and pushed gently posteriorly just enough to reposition the optic posterior to the iris. In some cases, pilocarpine 2% drops were utilized after the procedure to decrease the risk of recapture of the optic. Results: All 54 procedures were successfully performed in the office without significant pain or discomfort. Vision before optic capture, during optic capture, and at the first office visit after optic capture were comparable. There were not any cases of endophthalmitis, hyphema, iris trauma, iris prolapse or keratitis. While eight patients only had one episode of optic capture, 10 patients had multiple episodes of optic capture, all managed with this in office procedure. Recurrent optic capture occurred more frequently in eyes with fixation at less than 2 mm from the limbus than eyes with scleral fixation at 2 mm from the limbus. Conclusion: Reposition of the optic after pupillary capture of a scleral fixated PC IOL can be successfully performed in the office without discomfort or significant complications and is an alternative management option to a return to the operating room. This procedure may be especially important when there is poor access to the operating room or restricted access to the operating room as during the COVID19 pandemic.
by
Jessica Shantha;
Ian Crozier;
Colleen Kraft;
Donald G. Grant;
Augustine Goba;
Brent R. Hayek;
Caleb Hartley;
Kayla G. Barnes;
Timothy M. Uyeki;
John Schieffelin;
Robert F. Garry;
Daniel G. Bausch;
Paul E. Farmer;
John G. Mattia;
Matthew J. Vandy;
Steven Yeh
Background Following the West African Ebola virus disease (EVD) outbreak of 2013–2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. Methodology/Principal findings Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. Conclusions/Significance The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.
Recent Ebola epidemics, the ongoing COVID-19 pandemic, and emerging infectious disease threats have highlighted the importance of global infectious diseases and responses to public health emergencies. Ophthalmologists are essential health care workers who provide urgent and emergent vision care services during outbreaks and address the ocular consequences of epidemic and pandemic infectious diseases. In 2017, theWorld Health Organization (WHO) identified high priority pathogens likely to cause a future epidemic with the goal of guiding research and development to improve diagnostic tests, vaccines, and medicines. These measures were necessary to better inform and respond to public health emergencies.
Given the ocular complications associated with emerging infectious diseases, there is a need to recognize the ophthalmic sequelae for future vision health preparedness for potential future outbreaks. The WHO High Priority pathogens list provides a roadmap for ophthalmologists and subspecialty providers that will guide strategic areas of research for clinical care and preparedness for future pandemic threats. This review summarizes these key viral pathogens, summarizes major systemic disease findings, and delineates relevant ocular complications of the WHO High Priority pathogens list, including Crimean-Congo hemorrhagic fever, Filovirus diseases (Ebola virus disease and Marburg hemorrhagic fever), human Coronaviruses, Lassa Fever, Nipah virus infection, Zika, and Rift Valley fever.
by
Duncan E Berry;
Clay J Bavinger;
Alcides Filho Fernandes;
John Mattia;
Jalika Mustapha;
Lloyd Harrison-Williams;
Moges Teshome;
Matthew J Vandy;
Jessica Shantha;
Steven Yeh
The largest Ebola virus disease (EVD) outbreak occurred from 2013–2016 in West Africa, leading to over 28,600 cases and 11,300 deaths and resulted in the largest cohort of EVD survivors to date.1 Another recent outbreak in Democratic Republic of the Congo (DRC) has resulted in 3,481 cases with over 1,170 survivors since August 2018.2 In studies of large EVD survivor cohorts, uveitis is the most common ocular manifestation with a 13–34% reported prevalence.3,4 Cataract, with or without uveitis, is the second most common finding and has been reported in 10% of EVD survivors.3,4 The Ebola Virus Persistence in Ocular Tissues (EVICT) study was a cross-sectional study which supported the safety of cataract surgery in EVD survivors5, but may not be generalizable to vitreoretinal surgery. Posterior segment findings in EVD survivors have been described primarily in relationship to uveitis and include vitritis, chorioretinitis and chorioretinal scarring.3,6 The prevalence of posterior segment findings in EVD survivors, particularly those that may require surgical intervention, is of particular interest given the risk of Ebola virus (EBOV) persistence in ocular tissues and fluids.7
by
Jessica Shantha;
Dominick Canady;
Caleb Hartley;
Amy Cassedy;
Chris Miller;
Sheila T Angeles-Han;
Lloyd CM Harrison-Williams;
Matthew J Vandy;
Natalie Weil;
Gilberte Bastien;
Steven Yeh
Background: Ebola virus disease (EVD) outbreaks in West Africa (2013-2016) and the Democratic Republic of Congo (2018-2020) have resulted in thousands of EVD survivors who remain at-risk for survivor sequelae. While EVD survivorship has been broadly reported in adult populations, pediatric EVD survivors are under-represented. In this cross-sectional study, we investigated the prevalence of eye disease, health-related quality-of-life, vision-related quality-of-life, and the burden of mental illness among pediatric EVD survivors in Sierra Leone. Methods: Twenty-three pediatric EVD survivors and 58 EVD close contacts were enrolled. Participants underwent a comprehensive ophthalmic examination and completed the following surveys: Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale. Findings: A higher prevalence of uveitis was observed in EVD survivor eyes (10·8%) cohort compared to close contacts eyes (1·7%, p=0·03). Overall, 47·8% of EVD survivor eyes and 31·9% of close contact eyes presented with an eye disease at the time of our study (p=0·25). Individuals diagnosed with an ocular complication had poorer vision-related quality-of-life (p=0·02). Interpretation: Both health related quality-of-life and vision-related quality-of-life were poor among EVD survivors and close contacts. The high prevalence of eye disease associated with reduced vision health, suggests that cross-disciplinary approaches are needed to address the unmet needs of EVD survivors. Funding: National Institutes of Health R01 EY029594, K23 EY030158; National Eye Institute; Research to Prevent Blindness (Emory Eye Center); Marcus Foundation Combating Childhood Illness; Emory Global Health Institute; Stanley M. Truhlsen Family Foundation.